Cardiovascular Events in Men with Prostate Cancer Receiving Hormone Therapy: An Analysis of the FDA Adverse Event Reporting System (FAERS)

Abstract

Purpose:The comparative cardiovascular risk profiles of available hormone therapies for the treatment of prostate cancer is not known.Materials and Methods:We queried the U.S. Food and Drug Administration Adverse Event Reporting System, a retrospective, pharmacovigilance database, for cardiovascular adverse event reports in men with prostate cancer receiving gonadotropin releasing hormone (GnRH) agonists, GnRH antagonists, androgen receptor antagonists, and/or androgen synthesis inhibitors from January 2000 to April 2020.Results:Cardiovascular adverse events accounted for 6,231 reports (12.6%) on hormone monotherapy and 1,793 reports (26.1%) on combination therapy. Arterial vascular events were reported most commonly, followed by arrhythmias, heart failure, and venous thromboembolism. Compared to GnRH agonists, GnRH antagonists were associated with fewer cardiovascular adverse event reports as monotherapy (adjusted reporting odds ratio [ROR]=0.70 [95% CI 0.59–0.84], p <0.001) and as combination therapy (ROR=0.47 [0.34–0.67], p <0.0001), driven by reductions in arterial vascular events. Second generation androgen receptor antagonists and abiraterone were associated with more reports of hypertension requiring hospitalization (ROR=1.21 [1.03–1.41], p=0.02 and ROR=1.19 [1.01–1.40], p=0.03, respectively), and more heart failure events when used in combination with GnRH antagonists (ROR=2.79 [1.30–6.01], p=0.009 and ROR=2.57 [1.12–5.86], p=0.03).Conclusions:In this retrospective analysis of a pharmacovigilance database, arterial vascular events were the most commonly reported cardiovascular adverse events in men on hormone therapy for prostate cancer. GnRH antagonists were associated with fewer reports of overall cardiovascular events and arterial vascular events than GnRH agonists. Additional study is needed to identify optimal strategies to reduce cardiovascular morbidity among men with prostate cancer receiving hormone therapy.

Assessment and Mitigation of Cardiovascular Risk for Prostate Cancer Patients: A Review of the Evidence

“…The time from initiation of therapy to CV event was over 1-year (mean 541.9 days, SD 909.6) [ 28 ]. A similar study was carried out using the FDA Adverse Event Reporting System (FAERS) database [ 29 ]. Of 20 million CV events, 50, 000 were related to prostate cancer therapies.…”

“…GnRH antagonists were associated with fewer CV event reports (mainly arterial vascular events, venous thromboembolism, and arrhythmias) than GnRH agonists (Reporting Odds Ratio ROR = 0.70 [95% CI 0.59–0.84], p < 0.001). Further, a combination of GnRH agonists with any of the first- or second-generation androgen receptor inhibitors or abiraterone showed a 35% increase in the odds of a CV event compared to when they were used in combination with a GnRH antagonist ((arterial vascular events, e.g., MI/CAD/hypertension and arrhythmias) (ROR = 0.64 [0.54–0.81], p =0.0003)) [ 29 ].…”

Cardiovascular safety profile of taxanes and vinca alkaloids: 30 years FDA registry experience

“…The FAERS event report form for each patient consists of case identification number, suspected medication, the reason for use, adverse reactions, nature of the event (ie, serious vs non-serious), outcomes (hospitalisation, death and other outcomes), event date, the pharmaceutical company, reporter (eg, healthcare professional, consumer, a pharmaceutical company or unknown), concomitant medications and country of the event. 10 11 14 Age was tiered into 18–39, 40–59, 60–79 and ≥80 years.…”

“…It contains adverse event reports reported voluntarily for all marketed drug and therapeutic biologic products. [9][10][11] The informatic structure of the FAERS database abides by the international safety reporting guidance issued by the International Conference on Harmonisation (ICH E2B). Adverse events and medication errors are coded to terms in the Medical Dictionary for Regulatory Activities (MedDRA) terminology based on the broad Standardised MedDRA Query.…”

Androgen Deprivation Therapy, Hypogonadism and Cardiovascular Toxicity in Men with Advanced Prostate Cancer

“…Zhang et al [ 65 ] published recently a comparative cardiovascular risk profile of available ADT, by analyzing the FDA Adverse Events Reporting System (FAERS). They reviewed retrospectively the cardiovascular adverse effects which occurred in patients with prostate cancer treated with GnRH agonists, GnRH antagonists, androgen receptor antagonists and/or androgen synthesis inhibitors between January 2000 and April 2020.…”